IMPC Embryo Data

IMPC Viability

Category # Genes

viable

1796

lethal

663

subviable

276

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Each IMPC gene knockout strain is assessed for viability by examination of litters produced from mating heterozygous animals. A strain is declared lethal if no homozygous nulls pups are detected at weaning age. A strain is declared subviable if homozygous null pups constitute less than 12.5% of the litter. For lethal strains, embryos are phenotyped in the embryonic and perinatal lethal pipeline. For embryonic lethal and subviable strains, heterozygotes are phenotyped in the IMPC adult phenotyping pipeline.

IMPC Embryo Phenotyping - Goals and Procedures

With up to one third of knockout strains being embryonic lethal, a systematic unbaised phenotyping pipeline was established to perform morphologic and imaging evaluation of mutant embryos to define the primary perturbations that cause their death. From this important insights are gained into gene function.

IMPC centers funded by the NIH Common fund mechanism are delivering the following for All Lines:

  • Viability
  • Heterozygote E12.5 Embryonic LacZ staining ( 2 mutant animals, wt reference images)

For All Embryonic Lethal Lines, gross morphology is assessed at E12.5 to determine if defects occur earlier or later in development. A comprehensive imaging platform is then used to assess dysmorphology at the most appropriate stage:

ProcedureNumberNote
E9.5 Gross morphologyat least 2 homs,2 wtimages optional
E9.5 OPT screeningat least 2 homsreconstructions available
E14.5-E15.5 Gross morphologyat least 2 homs, 2 wtimages optional
E14.5-E15.5 microCT screeningat least 2 homsreconstructions available
E14.5 HREMat least 3 homs, 1wt reconstructions available
E18.5 Gross morphologyat least 2 homsimages optional
E18.5 microCTat least 2 homs, 2 wtreconstructions available

In addition, the NIH is supporting in-depth phenotyping of embryonic lethal lines with three current awardees.

Trevor William, University of Colorado School of Medicine

Jesse Mager, University of Massachusetts Amherst

Elizabeth Lacy, Memorial Sloan Kettering Cancer Center

Dr. Jeremy Reiter, University of California San Francisco

2D Imaging

Embryo LacZ

Tmem100

The majority of IMPC knockout strains replace a critical protein coding exon with a LacZ gene expression reporter element. Heterozygote E12.5 embryos from IMPC strains are treated to determine in situ expression of the targeted gene.

See all genes with embryo LacZ images.

Embryo Gross Morphology

  WT / Acvr2a

Gross morphology of embryos from lethal and subviable strains highlights which biological systems are impacted when the function of a gene is turned off. The developmental stage selected is determined by an initial assessment.

See embryo gross morphology images for E9.5, E12.5, E14.5-E15.5, E18.5.

3D Imaging

IEV

The embryonic and perinatal lethal pipeline comprises several 3D imaging modalities to quantify aberrant morphology that could not be determined by gross inspection. Images acquired by micro-CT and OPT are available via our Interactive Embryo Viewer (IEV).

Vignettes

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  • Chtop has been shown to recruit the histone-methylating methylosome to genomic regions containing 5-Hydroxymethylcytosine, thus affecting gene expression. Chtop mutants showed complete preweaning lethality with no homozygous pups observed. High resolution episcopic microscopy (HREM) imaging, revealed decreased number of vertebrae, abnormal joint morphology and edema. Full Analysis

    Chtoptm1a(EUCOMM)Wtsi

  • The Kldhc2 gene is located within a locus linked to an automsomal dominant disease that leads to fibro-fatty replacement of right ventricle myocardium leading to arrythmias (ARVD3 ; OMIM) Full Analysis

    Klhdc2tm1b(EUCOMM)Hmgu

  • Activin receptor IIA is a receptor for activins, which are members of the TGF-beta superfamily involved in diverse biological processes. Acvr2a mutants are subviable with most pups dying before postnatal day 7. Full Analysis

    Acvr2atm1.1(KOMP)Vlcg

  • Chromobox 4 is in the polycomb protein family that are key regulators of transcription and is reported to be upregulated in lung bud formation and required for thymus development Full Analysis

    Cbx4tm1.1(KOMP)Vlcg

  • Transmembrane Protein 100 functions downstream of the BMP/ALK1 signaling pathway. Tmem100 mutants showed complete preweaning lethality and were also lethal at E12.5. Full Analysis

    Tmem100tm1e.1(KOMP)Wtsi

  • Eyes absent transcriptional coactivator and phosphatase 4 is associated with a variety of developmental defects including hearing loss. Eya4 mutants showed complete preweaning lethality with no homozygous pups observed. Full Analysis

    Eya4tm1b(KOMP)Wtsi

  • Tox High Mobility Group Box Family Member 3 is a member of the HMG-box family involved in bending and unwinding DNA. Tox3 mutants have partial preweaning lethality with 1/3 of the pups dying before P7. Full Analysis

    Tox3tm1b(KOMP)Mbp

  • Radial spoke head protein 9 is a component of the radial spoke head in motile cilia and flagella. Rsph9 mutants showed partial pre-weaning lethality but viable to P7. Full Analysis

    Rsph9tm1.1(KOMP)Vlcg

  • Pax 7 is a nuclear transcription factor with DNA-binding activity via its paired domain. It is involved in specification of the neural crest and is an upstream regulator of myogenesis during post-natal growth and muscle regeneration in the adult. Full Analysis

    Pax7tm1.1(KOMP)Vlcg

  • Svep1 codes for an uncharacterized protein named after the multiple, extra-cellular domains identified in the sequence. Homozygotes fail between E18.5 and birth. Full Analysis

    Svep1tm1b(EUCOMM)Hmgu/J

  • Striatins act as both calcium-dependent signaling proteins and scaffolding proteins, linking calcium-sensing signaling events with cellular action. Lethality in Strn3 homozygotes occurs around E15.5. Full Analysis

    Strn3tm1b(KOMP)Wtsi/J

  • Rab34 is a member of the RAS oncogene family, involved in intracellular vesicle transport. Rab34 homozygotes are subviable at E18.5. Full Analysis

    Rab34tm1b(EUCOMM)Hmgu/J

  • Cytochrome c oxidase subunit VIIc (Cox7c) is a nuclear-encoded regulatory component of cytochrome c oxidase. Homozygous mutants do not survive between E15.5 and E18.5. Full Analysis

    Cox7ctm1b(KOMP)Mbp

  • Bloc1s2 functions in the formation of lysosome-related organelles through the BLOC-1 complex, with lethality occurring in knockouts around E15.5. Full Analysis

    Bloc1s2tm1.1(KOMP)Mbp

  • Solute carrier (metal ion transporter) family 39 member 8 (Slc39a8) mutants are small at E14.5 and show heart defects. Full Analysis

    Slc39a8tm1b(EUCOMM)Wtsi

  • Lysine (K)-specific demethylase 8 (Kdm8) is predicted to have dual functions as a histone demethylase and as a protein hydroxylase and is also known as Jmjd5. Tm1b mutants show developmental delay and fail to turn at E9.5. Full Analysis

    Kdm8tm1b(EUCOMM)Wtsi

  • Autophagy related 3 (Atg3) mutants show cardio-vascular defects at E14.5. Full Analysis

    Atg3tm1b(EUCOMM)Hmgu

  • Glutamine:fructose-6-phosphate amidotransferase 1 (Gfpt1) mutants show developmental delay and fail to turn at E9.5. Full Analysis

    Gfpt1tm1b(EUCOMM)Wtsi

  • Glycogenin is an enzyme that converts glucose to glycogen. Glycogenin catalyzes UDP-alpha-D-glucose + glycogenin ⇌ UDP + alpha-D-glucosylglycogenin. The enzyme is a homodimer of 37 kDa subunits. Mutations in human GYG1 are associated with Glyocgen Storage Disease XV and Polyglucosan Body Myopathy 2 (OMIM). Homozygous null Gyg mice die between birth and weaning but were found in normal proportions at E18.5. Mutants were indistinguishable from littermates at E12.5, E15.5 or E18.5 but analysis of microCT images revealed obvious cardiac abnormalities, enlarged thymus and abnormal nervous system morphology. This is the first reported Gyg mouse mutant. Full Analysis

    Gygtm1b(KOMP)Wtsi

  • Transmembrane protein132a is transmembrane protein of unknown function. Homozygous null mutants were viable at normal proportions at E15.5 and E18.5 but showed obvious and severe defects that were readibly visible by eye. Embryos had abnormal limb morphology with syndactyly, spina bifida, heart abnormalities. Some mutants were smaller than littermates. Full Analysis

    Tmem132atm1b(KOMP)Wtsi


These vignettes highlight the utility of embryo phenotyping pipeline and demonstrate how gross morphology, embryonic lacz expression, and high resolution 3D imaging provide insights into developmental biology. Clicking on an image will provide more information.

IMPC Embryonic Pipeline